Synthesis and separation of potential anticancer active dihalocephalomannine diastereomers from extracts of Taxus yunnanensis.
Two diastereomeric 2",3"-dibromo cephalomannines and their two corresponding 7-epimers were obtained by treatment of extracts of Taxus yunnanensis with bromine solution under mild conditions. Treatment of the same extract with chlorine solution yielded four diasteromeric 2",3"-dichlorocephalomannines, with no 7-epimers. The diastereomeric mixtures were separated into the individual components by preparative HPLC on C18 reversed-phase silica gel. A more efficient analytical separation was obtained on a pentafluorophenyl-bonded phase. These reaction products were isolated and fully identified spectroscopically. Slight differences were observed in the NMR spectra of the 7-epimers when compared to their 7 beta-OH analogues. On the basis of a comparison of physicochemical data, the bromo compounds were identified as (2"R,3"S)-dibromo-7-epi-cephalomannine (3), (2"S,3"R)-dibromo-7-epi-cephalomannine (4), (2"R,3"S)-dibromocephalomannine (5), and (2"S,3"R)-dibromocephalomannine (6), and the chloro compounds as (2"R,3"R)-dichlorocephalomannine (7), (2"S,3"S)-dichlorocephalomannine (8), (2"R,3"S)-dichlorocephalomannine (9), and (2"S,3"R)-dichlorocephalomannine (10). Cytotoxic activity was tested against the NCI 60 human tumor cell line panel in comparison with paclitaxel (1), and encouraging results were obtained in some cases.
Pandey
R C
RC
Xechem, Inc., Research Laboratories, New Brunswick, New Jersey 08901-3279, USA.
Yankov
L K
LK
Poulev
A
A
Nair
R
R
Caccamese
S
S
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D001966:Bromine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D009682:Magnetic Resonance Spectroscopy; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D013237:Stereoisomerism
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D001966:Bromine